Elucidation of molecular mechanisms in type 2 diabetes progression by novel insulin transcription factor
| Project/Area Number |
18K06134
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 43030:Functional biochemistry-related
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 2型糖尿病 / 糖毒性 / CPG16 / JDP2 / インスリン / 転写制御 / プロテインキナーゼ / インスリン発現 / 転写因子 |
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| Outline of Final Research Achievements |
Type 2 diabetes is exacerbated by hyperglycemia induced glucotoxicity, impairment of insulin secretion and suppression of insulin gene expression in pancreatic beta cells. We discovered novel signaling pathway involved in glucotoxicity such as candidate plasticity gene 16 (CPG16) and Jun dimerization protein 2 (JDP2) pathway. CPG16 suppressed up-regulation of insulin promoter activity by JDP2 through phosphorylation of Thr 116 in JDP2. Furthermore, JDP2 regulated activation and suppression of insulin gene expression via association of insulin transcription factors, MafA and ATF2. These results suggested that CPG16-JDP2 pathway may represent a therapeutic target in type 2 diabetes.
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| Academic Significance and Societal Importance of the Research Achievements |
日本人の2型糖尿病患者の多くはインスリンの分泌不全により病状が深刻化することが知られている。このインスリン分泌不全はインスリンの発現抑制によって引き起こされる。本研究で我々は、インスリン発現抑制に関連する新規シグナル経路としてCPG16-JDP2経路を発見した。この経路はインスリン発現のONとOFFを司ることからインスリンの発現制御機構を明らかにする上で重要であると考えられる。また、深刻な2型糖尿病患者の治療における分子標的として期待される。
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Thyroid stimulating hormone stimulates the expression of glucose transporter 2 via its receptor in pancreatic β cell line, INS-1 cells.2018
Author(s)
Lyu J, Imachi H, Yoshimoto T, Fukunaga K, Sato S, Ibata T, Kobayashi T, Dong T, Yonezaki K, Yamaji N, Kikuchi F, Iwama H, Ishikawa R, Haba R, Sugiyama Y, Zhang H, Murao K.
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Journal Title
Sci Rep.
Volume: 8
Issue: 1
Pages: 1986-1995
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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